Nanosecond pulse generator with a protector circuit

ABSTRACT

This invention relates to a pulse generator circuit for delivering a short high current pulse to a load. This pulse generator comprises a junction recovery diode, a switch, a first resonant circuit and a second resonant circuit. The diode may be configured to store charges in its depletion layer when there is a forward flow of a current and to rapidly switch open after the depletion layer is discharged by a reverse flow of a current. After the diode rapidly switch opens, the pulse generator may provide a reverse current to the load. This pulse generator may be configured to generate at least one pulse that is having a length of no more than 100 nanoseconds at the full-width-at-half-maximum and an amplitude of at least 1 kilovolt. Electrodes may be connected to the pulse generator to deliver one pulse or plurality of pulses to biological cells such as tumor cells.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.12/471,229, filed May 22, 2009, attorney docket no. 64693-233, entitled“Nanosecond Pulse Generator,” which claims priority to U.S. ProvisionalApplication Ser. No. 61/128,708, filed May 23, 2008, attorney docket no.64693-217, entitled “Nanosecond Aircore Pulse Generator with ScalablePulse Amplitude.” The entire content of both applications isincorporated herein by reference.

STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH

This invention was made with government support under Contract No.F49620-02-1-0073 awarded by the U.S. Air Force Office of ScientificResearch. The government has certain rights in the invention.

FIELD OF THE INVENTION

This invention relates to pulse generators and, more particularly, topulse generators that may be used for electroperturbation of biologicalcells.

BACKGROUND OF THE INVENTION

Ultra-short, high-field strength electric pulses may be used in theelectroperturbation of biological cells. For example, these electricpulses may be used in treatment of human cells and tissue includingtumor cells, such as basal cell carcinoma, squamous cell carcinoma andmelanoma. For in detail discussion of such applications, for example,see, Garon et al. “In Vitro and In Vivo Evaluation and a Case Report ofIntense Nanosecond Pulsed Electric Field as a Local Therapy for HumanMalignancies”, Int. J. Cancer, vol. 121, 2007, pages 675-682.

The voltage induced across a cell membrane may depend on the pulselength and pulse amplitude. Pulses longer than about 1 microsecond maycharge the outer cell membrane and lead to opening of pores, eithertemporarily or permanently. Permanent openings may result in cell death.

Pulses much shorter than about 1 microsecond may affect the cellinterior without adversely affecting the outer cell membrane. Suchshorter pulses with a field strength varying in the range of 1 MV/m to10 MV/m may trigger apoptosis or programmed cell death. Higher amplitudeand shorter electric pulses are useful in manipulating intracellularstructures such as nuclei and mitochondria.

Spark gap switched transmission lines have been used to generateultra-short pulses. However, they may be physically large and have onlya low repetition rate. They may also have only a relatively shortlifetime, and provide erratic pulses with a large amount of jitter. Thetransmission line capacitance may also need to be charged rapidly inorder to overvolt the spark gap to meet a fast rise time requirement.

Radio frequency metal-oxide semiconductor field effect transistor(MOSFET) switched capacitors have also been used to generate ultra-shortpulses. However, MOSFET switched capacitors may not be able to generatepulses with lengths narrower than 15-20 nanoseconds. This may be due tocomplications of MOSFET driving circuits and inherent limitations ofmany MOSFET devices.

Nanosecond high voltage based pulse generators based on diode openingswitches have also been proposed for biological and medicalapplications. For example see: Gundersen et al. “Nanosecond PulseGenerator Using a Fast Recovery Diode”, IEEE 26^(th) Power ModulatorConference, 2004, pages 603-606; Tang et al. “Solid-State High VoltageNanosecond Pulse Generator,” IEEE Pulsed Power Conference, 2005, pages1199-1202; Tang et al. “Diode Opening Switch Based Nanosecond HighVoltage Pulse Generators for Biological and Medical Applications”, IEEETransactions on Dielectrics and Electrical Insulation, Vol. 14, No. 4,2007, pages 878-883; Yampolsky et al., “Repetitive Power Pulse GeneratorWith Fast Rising Pulse” U.S. Pat. No. 6,831,377; Gundersen et al.,“Method for Intracellular Modifications Within Living Cells Using PulsedElectric Fields”, U.S. Patent Publication No. 2006/0062074; Kuthi etal., “High Voltage Nanosecond Pulse Generator Using Fast Recovery Diodesfor Cell Electro-Manipulation”, U.S. Patent Publication No.2007/0031959; and Krishnaswamy et al., “Compact Subnanosecond HighVoltage Pulse Generation System for Cell Electro-Manipulation”, U.S.Patent Publication No. 2008/0231337.

The diode opening switches may operate at two different modes. The firstmode is called junction recovery (JR) mode and the second mode siliconopening switch (SOS) mode. For in detail description of diode openingswitches, for example, see: Moll et al., “Physical Modeling of the Pulseand Harmonic Step Recovery Diode for Generation Circuits”, Proceedingsof the IEEE, vol. 57, no. 7, 1969, pages 1250-1259; Hewlett PackardApplication Note 918, “Pulse and Waveform Generation with Step RecoveryDiodes”; Kotov et al., “A Novel Nanosecond Semiconductor Opening Switchfor Megavolt Repetitive Pulsed Power Technology: Experiment andApplications,” Proc. 9^(th) Int. IEEE Pulsed Power Conf., Albuquerque,N. Mex., 1993, pages 134-139; Lyubutin et al., “Repetitive NanosecondAll-Solid-State Pulsers Based on SOS Diodes”, IEEE 11^(th) Intern.Pulsed Power Conf., Baltimore, Md., 1997, pages 992-998; Rukin,“High-Power Nanosecond Pulse Generators Based on Semiconductor OpeningSwitches”, Instruments and Experimental Techniques, vol. 42, No. 4,1999, pages 439-467; and Grekhov et al., “Physical Basis for High-PowerSemiconductor Nanosecond Opening Switches,” IEEE Transactions on PlasmaScience, vol. 28, 2000, pages 1540-1544.

SUMMARY

This invention relates to a pulse generator circuit for delivering ashort high current pulse to a load. This pulse generator comprises ajunction recovery diode, a switch, a first resonant circuit and a secondresonant circuit.

These components of the electric circuit may be configured as follows.The diode may be configured to store charges in its depletion layer whenthere is a forward flow of a current and to rapidly switch open afterthe depletion layer is substantially discharged by a reverse flow of acurrent. The switch may be configured to allow storage of energy from asource when it is opened and to allow the forward current flow after itis closed. The first resonant circuit may be configured to store energyfrom a source when the switch is opened and to provide the forward flowof the current through the diode after the switch is closed, therebycharging the depletion layer of the diode. The second resonant circuitmay be configured to store the energy transferred from the firstresonant circuit after the switch is closed and to provide the reverseflow of the current through the diode until the depletion layer of thediode is substantially discharged, thereby causing the diode to rapidlyswitch open, and thereafter to provide a reverse current to the load.

This pulse generator may be configured to cause the charges stored inthe depletion layer of the diode to be substantially discharged when thepeak current flowing through the second resonant circuit issubstantially higher than the peak current that previously flowedthrough the first resonant circuit. The pulse generator may even beconfigured to cause the charges stored in the depletion layer of thediode to be substantially discharged when the ratio of the peak of thereverse flow of the current to the peak of the forward flow of thecurrent is substantially approaching to two.

A diode that has suitable charge storage characteristics and a veryshort snap-off time may be suitable for the pulse generators of theinstant invention. For example, the diode of this pulse generator may bea diode operating in a junction recovery mode. This diode may also be adiode operating in a silicon opening switch mode. This diode may even bea combination of diodes operating in the junction recovery mode or thesilicon opening switch mode.

The diode of the instant invention may have a junction recovery timelonger than 10 nanoseconds. This junction recovery time may even belonger than 25 nanoseconds. This diode may be configured to have asnap-off time shorter than 10 percent of its junction recovery time.This diode may even be configured to store charges in its depletionlayer with an amount higher than one micro-coulomb.

The first resonant circuit of the pulse generator of the instantinvention or the second resonant circuit may comprise an inductor. Thisinductor may be an air-core inductor, a linear-magnetic-core inductor, asaturable-magnetic-core inductor or combinations thereof. All possiblecombinations of these inductor types may be useful for construction ofthe inductor of the first resonant circuit and/or the second resonantcircuit. All such combinations are within the scope of this invention.For example, the inductor of the first resonant circuit may be anair-core inductor and that of the second resonant circuit may be asaturable-magnetic-core inductor. Alternatively, the inductor of thefirst resonant circuit may be a saturable-magnetic-core inductor and theinductor of the second resonant circuit may be an air-core inductor. Itis also within the scope of this invention that the inductor of thefirst resonant circuit may be a saturable-magnetic-core inductor andthat of the second resonant circuit may be a saturable-magnetic-coreinductor.

The pulse generator of the instant invention may be configured such thatthe resonant frequency of the first resonance circuit and the resonantfrequency of the second resonance circuit are substantially the same.The pulse generator of the instant invention may also be configured suchthat the resonant frequency of the first resonance circuit and theresonant frequency of the second resonance circuit are substantiallydifferent.

The switch of the pulse generator of the instant invention may have aturn-on time of less than 100 nanoseconds. This switch may be ametal-oxide semiconductor field effect transistor (MOSFET) switch,integrated gate bipolar transistor (IGBT) switch, bipolar junctiontransistor (BJT) switch, silicon controlled rectifier (SCR) switch, gasdischarge switch, or combinations thereof.

The pulse generator of the instant invention may further comprise acurrent limiting resistor configured to limit damage to the pulsegenerator circuit. This pulse generator may also further comprise atransformer configured to isolate the pulse generator circuit. Thispulse generator may even further comprise a terminating resistance inparallel with the diode that is configured to protect the output stageof the pulse generator.

The pulse generator of the instant invention may be configured togenerate at least one pulse that is having a length of no more than 100nanoseconds at the full-width-at-half-maximum and an amplitude of atleast 1 kilovolt.

This pulse generator may be used for electroperturbation of biologicalcells and also in treatment of human cells and tissue including tumorcells, such as basal cell carcinoma, squamous cell carcinoma andmelanoma.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 illustrates an example of the pulse generator of the instantinvention.

FIG. 2 illustrates the forward current flowing through the diode D for aperiod of T_(F) and the reverse current flowing through the diode for aperiod of T_(JR).

FIG. 3 illustrates an example of the pulse generator of the instantinvention.

FIG. 4 illustrates an example of the pulse generator of the instantinvention.

FIG. 5 illustrates an example of the pulse generator of the instantinvention.

FIG. 6 shows the variation of the calculated short circuit current withtime.

FIG. 7 compares variation of the peak current of five commercialswitches that may be used as the switch S with the input voltage.

FIG. 8 shows the variation of the pulse amplitude with the input voltageV_(in) for two examples of the pulse generator of the instant invention.

FIG. 9 shows the variation of the measured short circuit current withtime.

FIG. 10 compares the measured current flowing through the diode with themeasured short circuit current.

FIG. 11 shows the variation of the output pulse voltage with time.

FIG. 12 shows the variation of the output pulse voltage with time.

FIG. 13 shows the variation of the output pulse voltage with time for 25repetitive pulse outputs.

FIG. 14 shows the variation of the pulse amplitude with the inputvoltage V_(in).

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

This invention relates to a pulse generator circuit for delivering ashort high current pulse to a load. This pulse generator may include ajunction recovery diode, a switch, a first resonant circuit and a secondresonant circuit. This pulse generator may be used forelectroperturbation of biological cells. This pulse generator may beused in treatment of human cells and tissue including tumor cells, suchas basal cell carcinoma, squamous cell carcinoma and melanoma.

The components of the electric circuit may be configured as follows. Thediode may be configured to store charges in its depletion layer whenthere is a forward flow of a current and to rapidly switch open afterthe depletion layer is substantially discharged by a reverse flow of acurrent. The first resonant circuit may be configured to store energyfrom a source when the switch is opened and to provide the forward flowof the current through the diode when the switch is closed, therebycharging the depletion layer of the diode. The second resonant circuitmay be configured to store the energy transferred from the firstresonant circuit after the switch is closed and to provide the reverseflow of the current through the diode until the depletion layer of thediode is substantially discharged, thereby causing the diode to rapidlyswitch open, and thereafter to provide a reverse current to the load.

FIG. 1 schematically shows a simplified pulse generator of the instantinvention by way of example. In this pulse generator, the diode D may beconfigured to operate as an opening switch. The first resonant circuitcomprises a first capacitor C₁ and a first inductor L₁, and the secondresonance circuit comprises a second capacitor C₂ and a second inductorL₂.

In this example, this pulse generator circuit may be connected to apower source depicted as V_(in) through a resistor R_(ch). The pulsegenerated by the pulse generator of the instant invention may betransferred to a resistive load depicted as R_(L). This load may be atumor cell.

At the beginning of a pulse cycle, the switch S may be opened. This mayallow the capacitance C₁ to be substantially charged by the power sourceV_(in). After the capacitance C₁ is substantially charged, the switch Smay be closed. This may cause charges to transfer from the capacitanceC₁ to the capacitance C₂ and thereby forming a forward flow of currentthrough the diode D. During this transfer, the current through thecircuit may rise and fall in approximately a sinusoidal manner. Thiscurrent may cause the diode D to be forward-biased as it travels throughit. During this process, charges may be stored in the depletion layer ofthe diode D.

After the capacitance C₂ is charged, the current flow may reverse due tothe second resonant circuit. Since the depletion layer of the diode D ischarged, the reverse current may flow through the diode D for a periodof time. The reverse current flow eventually may substantially dischargethe diode D and may result in an abrupt rise in its resistance. Thissudden resistance rise occurring in a very short period of time mayprevent further flow of the current in the reverse direction through thediode D and may provide the energy stored in the inductor L₂ to the loadR_(L) in the form of an electrical pulse.

After the pulse is delivered to the load R_(L) the switch S may beopened to charge the capacitor C₁ to initiate another pulse cycle. Thus,the pulse generator of the instant invention may deliver one pulse ormore than one pulse repetitively.

During the pulse delivery process, the diode D may act like a switch.That is, when there is a forward current, it may allow the current topass through the circuit in forward direction, thereby acting like aswitch that is closed. When the current is reversed, it may allow areverse current through its cathode and anode for a period of time.Then, the diode may prevent this reverse current after its depletionlayer is substantially discharged, thereby acting like a switch that isopened.

A diode that can allow this reverse current for a period of time and canprevent the reverse current after this period of time within a veryshort duration of time is within the scope of this invention. The periodof time during which a reverse current is allowed through the diode D iscalled the “junction recovery time” hereafter. The duration of time,occurring after the junction recovery time, during which the resistanceof the diode D substantially increases, thereby preventing the furtherflow of current, is called the “snap-off time”. A diode that can have asuitable junction recovery time and a very short snap-off time is withinthe scope of this invention. For example, the diode of the instantinvention may have a junction recovery time longer than 10 nanoseconds.The junction recovery time may even be longer than 25 nanoseconds. Thesnap-off time may be shorter than 10 percent of the junction recoverytime. For example, the junction recovery time may be shorter than 2.5nanoseconds or even shorter than 1 nanosecond. This may be a diode thatcan store charges in its depletion layer with an amount higher than onemicro-coulomb.

The diodes of the instant invention may be substantially charged duringthe forward current flow within a period of time, which is called the“diode saturation time” hereafter. Suitable diodes may be substantiallycharged within a reasonably short diode saturation time. A suitablediode saturation time may be shorter than 100 nanoseconds.

Examples of such diodes are junction recovery diodes, junction recoverydrift diodes, snap recovery diodes, opening switch diodes, step recoverydiodes or the like. They are all within the scope of this invention.Such diodes are going to be called as the “junction recovery diodes”hereafter. The junction recovery diodes may have two different principlemodes of operation. The first mode is called junction recovery (JR)mode. When operated in this mode, the diodes stop conducting due torecovery of the PN-junction blocking capability. The second mode iscalled silicon opening switch (SOS) mode. For this mode, the junctiondoes not recover, but the majority of the current is provided to theload R_(L) due to a drastic increase in resistance of the low-doped partof the P-layer.

The junction recovery diodes operating in the JR mode may have a shortersnap-off time and dissipate less energy during the switching process.However, the JR mode diodes may not be able to switch as high energiesas the SOS mode diodes can. Some applications of the pulse generators ofthe instant invention may require shorter snap-off times. For suchapplications relatively low energy pulses may be sufficient. Such pulsegenerators may use the JR mode diodes. For other applications, thatrequire higher energy pulses, but still tolerate longer snap-off times,the SOS mode diodes may be used. Yet for some applications, the JR modediodes may be used in combination with the SOS mode diodes to remedy theshortcoming of each diode type. Thus, the JR mode diodes, the SOS modediodes and combinations thereof are all within the scope of thisinvention.

The junction recovery diodes may be custom designed and manufactured tosuit requirements of the instant invention. These diodes may also bechosen among commercially available diodes. Not every commerciallyavailable diode may be used to construct the pulse generator of theinstant invention. To use a commercial diode that is suitable as ajunction recovery diode, several commercially available diodes may bepurchased and then experimentally tested for their junction recoverytime and snap-off time. The commercial diodes that are found byexperimentation to have a suitable junction recovery time and a veryshort snap-off time may be used in the construction of the pulsegenerators. There might be many examples of such commercial diodes. Oneexample of such diode is commercially available from EIC Semiconductor(Irwindale, Calif.) with a model number EIC CN25M diode, which has a DCrating of about 1 kilovolt (kV) and about 25 amperes. The junctionrecovery time for this diode is about 50 nanoseconds. Another example ofsuch diodes is commercially available from Vishay (Shelton, Conn.) witha model name MURS360, which is rated at about 600 V and about 3 amperesand which has about 75 nanoseconds junction recovery time.

One or more than one diode may be used in the construction of the pulsegenerator. For example a diode array may be used as the junctionrecovery diode D. The diode array may comprise more than one diode inparallel and/or more than one diode in series. Connecting diodes inparallel may distribute the forward current across the diodes in thearray, thus increasing the amount of time that current may be sentthrough the array before the diodes become fully charged, i.e.saturated. Connecting diodes in series (i.e. diode stack) in an arraymay increase the amount of voltage that may be applied to the diodeswhen the current flow is reversed, that is the diodes arereverse-biased. This may allow the output voltage of the pulse generatorto be greater. The number of diodes that are placed in parallel and/orin series may be any number, so long as at least one diode is used.Using too many diodes may increase the capacitance of the circuit andslow its performance.

In order to use the diode D as an opening switch and to be able todeliver maximum energy to the load R_(L), it may be forward and reversepumped by an appropriate sinusoidal current to ensure that it quitsconducting when the majority of the total energy is stored in L₂. FIG. 2illustrates the appropriate current waveform that may flow through thediode D to provide a proper operation. During the forward flow ofcurrent, i.e. the forward pumping period, T_(F), the diode D may beforward biased and charges may be stored in its depletion layer. Asexplained above, once the current has reversed, and the charges arewashed out of the junction, i.e. at the end of the junction recoverytime, the diode D may stop conducting and the reverse current flowingthrough the diode may be provided to the load R_(L). The junctionrecovery time is shown as T_(JR) in FIG. 2. The snap-off time may bevery small as compared to the junction recovery time and not identifiedin FIG. 2.

If the diode D switches open when the reverse current is at a maximum,the shaded area under the curve in FIG. 2 may be equal to the area underthe curve during the forward pumping period, T_(F). For this condition,the reverse current peak I_(MAX) may be twice the forward current peakW_(IN). Or in other words, the ratio of the peak of the reverse currentto the peak of the forward current or the current ratio=I_(MAX)/I_(MIN)may be two. The pulse generators that are configured to have the currentratio of two are within the scope of this invention.

However, construction of a pulse generator configured to have thecurrent ratio of two may increase its production and operation costs.These costs may be decreased by having pulse generators configured tohave the current ratio substantially approaching two. These costs mayalso be decreased by having pulse generators configured to cause thecharges stored in the depletion layer of the diode to be discharged whenthe energy stored in the second resonant circuit is substantially higherthan the energy stored in the first resonant circuit.

For example, the values of circuit components forming the pulsegenerator shown in FIG. 1 may be selected so as to cause the charge inthe diode D to be depleted at approximately the peak of the reverse biascurrent during the second half of the pulse cycle. When this occurs, thecurrent through the load R_(L) may be at maximum at the moment the diodeD switches open, thus maximizing the peak voltage across the load R_(L).In one example, to affect this peak timing, the values of capacitancesC₁ and C₂ may be chosen to be substantially the same and the inductancesL₁ and L₂ may be chosen to be substantially the same.

Furthermore, the resonant frequency of both resonant circuits may besubstantially the same. Such frequencies are within the scope of thisinvention. There might be other values for capacitances and inductancesof the resonant circuits for which the resonant frequencies of thesecircuits might be different. Such resonant frequencies are also withinthe scope of this invention.

Any type of inductor may be used in construction of the pulse generator.For example, air-core type inductors, linear-magnetic-core typeinductors (i.e. inductors with magnetic-cores that are operated withinthe linear region of their hysteresis curve), saturable-magnetic-coretype inductors or their combinations may be used. The air-core inductorsor the linear-magnetic-core inductors may have several advantages overthe saturable-magnetic-core inductors. The air-core inductors or thelinear-magnetic-core inductors allow the adjustment of the pulseamplitude independent of the pulse length. The air-core inductors or thelinear-magnetic-core inductors are also free of the jitters, which arepulse to pulse variations of pulse amplitude or period, caused by havingsaturable-magnetic-cores. As a result, a simpler and smaller pulsegenerator may be constructed by using the air-core inductors or thelinear-magnetic-core inductors. However, it might be difficult toscale-up the pulse generators that use the air-core inductors or thelinear-magnetic-core inductors to operate relatively higher voltages anddeliver higher energy pulses. Although the higher voltage pulsegenerators may be constructed by using the air-core inductors or thelinear-magnetic-core inductors, they may require more complicatedcircuitry at relatively higher voltages.

The saturable-magnetic-core inductors may have several advantages overthe air-core inductors or the linear-magnetic-core inductors. They maybe very suitable for construction of higher voltage pulse generatorsbecause of their ability to switch relatively higher currents. They mayrepeatedly achieve higher current operation with relatively lessdegradation in their performance. However, they may also havedisadvantages. For example, the saturable-magnetic-core inductors mayintroduce amplitude jitter that may be attributed to the BH hysteresisinherent to their magnetic cores. Adding a constant core bias maymitigate the jitter; however this extra circuitry may increasecomplexity of the pulse generator and may reduce overall efficiency.

Thus, the air-core inductors, the saturable-magnetic-core inductors andthe saturable-magnetic-core inductors are all have advantages as well asdisadvantages as compared to each other. In some applications, whichrequire pulse generators with relatively free of jitter and with simplerand smaller constructions, but tolerate lower energy pulses, theair-core inductors or the linear-magnetic-core inductors may be used. Inother applications, which require higher energy pulse generators, butafford more complex circuitry, the saturable-magnetic-core inductors maybe used. Yet in other applications, the air-core inductors, thelinear-magnetic-core inductors and the saturable-magnetic-core inductorsmay be used in combination to remedy the shortcomings of each inductortype when used alone.

Thus, the air-core inductors, the linear-magnetic-core inductors, thesaturable-magnetic-core inductors and combinations thereof may be usedin the construction of the pulse generators of the instant invention.For example, the inductor of the first resonant circuit may be anair-core inductor, a linear-magnetic-core inductor, asaturable-magnetic-core inductor or combinations thereof. Similarly, theinductor of the second resonant circuit may be an air-core inductor, alinear-magnetic-core inductor, a saturable-magnetic-core inductor orcombinations thereof. For example, the inductors L₁ and L₂ may be bothair-core inductors. They may also be both saturable-magnetic-coreinductors. Or, L₁ may be an air-core inductor and L₂saturable-magnetic-core inductor. Or, L₁ may be asaturable-magnetic-core inductor and L₂ may be an air-core inductor.Thus, all possible combinations of these inductor types are useful forconstruction of the first inductor and/or the second inductor of thepulse generators of the instant invention and they are all within thescope of this invention.

In order to create very short pulses, the switch S may need to open andclose very quickly. Thus, any switch that can open and close veryquickly is suitable for the pulse generator of the instant invention.Examples of such switches may be metal-oxide semiconductor field effecttransistor (MOSFET) type switches, (silicon controlled rectifier) SCRtype switches, bipolar junction transistor (BJT) type switches,integrated gate bipolar transistor (IGBT) type switches, gas dischargetype switches and combinations thereof. Even mechanical relays may beused to construct the switch S.

Any type of MOSFET switch may be used. For example, a MOSFETmanufactured by Microsemi Corporation (Irvine, Calif.) with a modelnumber APT37M100L MOSFET and with a DC rating of 1,000 V and 37 amperesmay be used as the switch S. The MOSFET may be driven by any suitablepower supply (not shown in FIG. 1).

The pulse generator of the instant invention may include a currentlimiting resistor R_(d) configured to limit damage to the pulsegenerator circuit. This construction of the pulse generator isillustrated in FIG. 3 by way of example. In this example, the currentlimiting resistor R_(cl) is configured to protect the diode S. Thiscurrent limiting resistor R_(cl) may be configured to limit damage toany component of the pulse generator.

For example, the current flowing through a diode array may not be evenlydistributed among the diodes. This might be due to imperfectlymanufactured components of the pulse generator or even imperfectlymanufactured pulse generator. This might also be due to current orvoltage fluctuations occurring during the operation of the pulsegenerator. If the current is not evenly distributed among the diodesforming the array, one of these diodes may fail, eventually damaging thewhole array or the pulse generator. To prevent such damages a currentlimiting resistor may be connected in series to each diode or each diodestack.

The pulse generator of the instant invention may include a transformerT_(x) configured to isolate the pulse generator circuit. Thisconstruction of the pulse generator is illustrated in FIG. 4 by way ofexample. The accidental discharge of electricity, for example to aliving body, from the pulse generator is prevented by using thistransformer.

The pulse generator of the instant invention may include a terminatingresistance R_(T) in parallel with the diode S configured to protect theoutput stage of the pulse generator. This construction of the pulsegenerator is illustrated in FIG. 5 by way of example. If the load R_(L)becomes too high, the terminating resistance R_(T) may serve to lowerthe load impedance seen by the output stage (for example, by the diodeS) thereby limiting over voltages and protecting the circuit. Value ofthis resistance may be any value that can protect the circuit withoutexcessively limiting the output pulse characteristics. For example, thevalue of the terminating resistance may be equal to or many times higherthan anticipated level of the load R_(L). For example, the value of theterminating resistance may be higher than 10 ohms. For example, thevalue of the terminating resistance may be as high as 10 kilo-ohms.

The pulse generator of the instant invention may include the currentlimiting resistor R_(cl), the transformer T_(x) and the terminatingresistance R_(T) alone or in combination. For example, the pulsegenerator may include a current limiting resistor R_(cl) and atransformer T_(x). In another example, the pulse generator may include acurrent limiting resistor R_(cl), a transformer T_(x) and a terminatingresistance R_(T). All such combinations are within the scope of thisinvention.

The pulse generators of the instant invention may generate at least onepulse that is having a length of no more than 100 nanoseconds at thefull-width-at-half-maximum (FHWM) and an amplitude of at least 1 kV.These generators may deliver pulses with FHWMs varying in the range of 2nanoseconds to 10 nanoseconds. They may even deliver pulses with FHWMsvarying in the range of 2 nanoseconds to 5 nanoseconds. The pulseamplitude of these generators can be scaled with the input voltageV_(in). For example, they can provide pulse amplitudes in the range of0.5 kV to 7.0 kV by increasing the input voltage V_(in) in the range of100 V to 1000 V.

Even higher amplitudes may be reached by designing a more complicatedswitch array, such as a Marx array, that will allow higher current andvoltage ratings. In this way, the output amplitude may be scaled to alevel even higher than 7.0 kV. The upper amplitude level may be limitedby electric breakdown strength of insulators, parasitic capacitance andinductance associated with the switch bank and/or similar electricalproblems.

The pulse generators of the instant invention may include electrodes todeliver one or plurality of pulses to biological cells such as humancells and tissue including tumor cells, such as basal cell carcinoma,squamous cell carcinoma and melanoma.

The invention is illustrated further by the following additionalexamples that are not to be construed as limiting the invention in scopeto the specific procedures or products described in them.

Example 1 Resonant Network Design

In this example, the values of the capacitors and inductors may bedetermined by using a mathematical model for the circuit shown in FIG. 1as follows. The diode D may be approximated as lossless with a givenjunction recovery time of about 50 nanoseconds. Then, the forward biaseddiode may be modeled as an ideal voltage source with a voltage equal tothe forward voltage of the diode. This model may be valid until thereverse current flows through the diode for a period equal to thejunction recovery time. At this time the conductivity of the losslessdiode instantaneously may go to zero. Since the forward biased diode maybe modeled as having zero impedance, the diode may be replaced by ashort circuit to derive a mathematical model for the current. Thisexpression may be used as a guide to choose inductance and capacitancevalues that produce an appropriate current to ensure proper switching ofthe diode (i.e. substantially satisfying I_(MAX)=2*I_(MIN)). Thefollowing equation was derived by solving for the short circuitcurrent's step response in the s-domain and then using an inverseLaplace transform to obtain a time-domain expression:

$\begin{matrix}{{i_{sc}(t)} = {\frac{V_{o}}{{kL}_{1}}\left\lbrack \frac{{\omega_{1}{\sin \left( {\omega_{1}t} \right)}} - {\omega_{2}{\sin \left( {\omega_{2}t} \right)}}}{\omega_{1}^{2} - \omega_{2}^{2}} \right\rbrack}} & (1) \\{\omega_{1}^{2} = {\frac{\omega_{o}^{2}}{2{kn}}\left\lbrack {1 + {n\left( {1 + k} \right)} + \sqrt{({kn})^{2} + {2{{kn}\left( {n - 1} \right)}} + \left( {n + 1} \right)^{2}}} \right\rbrack}} & (2) \\{\omega_{2}^{2} = {\frac{\omega_{o}^{2}}{2{kn}}\left\lbrack {1 + {n\left( {1 + k} \right)} - \sqrt{({kn})^{2} + {2{{kn}\left( {n - 1} \right)}} + \left( {n + 1} \right)^{2}}} \right\rbrack}} & (3) \\{\omega_{o} = \frac{1}{\sqrt{L_{1}C_{1}}}} & (4)\end{matrix}$

where i_(sc) is the current flowing through the diode, wherein the diodeis approximated as a short circuit, V_(o) is the initial voltage storedin the first capacitor C₁, k is the ratio L₂/L₁, and n is the ratioC₂/C₁.

When the diode quits conducting, it may be important not only that thepeak current is maximized, but also that the majority of the energyinitially stored in the capacitor C₁ is transferred to the inductor L₂.If energy remains in the other inductor or capacitors, then it maycontinue to resonate in the system and will be dissipated into the loadR_(L) some time after the pulse is delivered. To prevent this, thevalues of the circuit components are chosen such that the energy storedin inductor L₁ and capacitors C₁ and C₂ is at a minimum when the diodestops conducting. The following equations may be used to find the energystored in different circuit components when the diode stops conducting:

$\begin{matrix}{{i_{L\; 1}(t)} = {\frac{V_{o}}{L_{1}}\left\lbrack \frac{{{\omega_{2}\left( {\omega_{1}^{2} - \frac{\omega_{0}^{2}}{nk}} \right)}{\sin \left( {\omega_{1}t} \right)}} + {{\omega_{1}\left( {\frac{\omega_{0}^{2}}{nk} - \omega_{2}^{2}} \right)}{\sin \left( {\omega_{2}t} \right)}}}{\omega_{1}{\omega_{2}\left( {\omega_{1}^{2} - \omega_{2}^{2}} \right)}} \right\rbrack}} & (5) \\{{v_{L\; 1}(t)} = {V_{o}\left\lbrack \frac{{{\omega_{2}\left( {\omega_{1}^{2} - \frac{\omega_{0}^{2}}{nk}} \right)}{\cos \left( {\omega_{1}t} \right)}} + {\left( {\frac{\omega_{0}^{2}}{nk} - \omega_{2}^{2}} \right){\cos \left( {\omega_{2}t} \right)}}}{\omega_{1}^{2} - \omega_{2}^{2}} \right\rbrack}} & (6) \\{{v_{L\; 2}(t)} = {V_{o}\left\lbrack \frac{{\omega_{1}^{2}{\cos \left( {\omega_{1}t} \right)}} - {\omega_{2}^{2}{\cos \left( {\omega_{2}t} \right)}}}{\omega_{1}^{2} - \omega_{2}^{2}} \right\rbrack}} & (7)\end{matrix}$

where L_(i) is the current through L₁, V_(L1) is the voltage across L₁,and V_(L2) is the voltage across L₂; ω₁, ω₂, and ω₀ are given byequations 2, 3, and 4 respectively. By using above equations, theinstantaneous energy stored in both inductors and both capacitors can bedetermined. These equations can simultaneously be solved with equation 1to ensure that the majority of energy is stored in L₂ when the diodeswitches open.

A commercially available mathematical software, MATLAB was used to solveabove equations. The results are schematically shown in FIG. 6. For thejunction recovery time of about 50 nanoseconds, for I_(MAX)≈2*I_(MIN)and for the capacitors and inductors with the same values, it wasdetermined that L₁=L₂= about 260 nanoHenry (nH) and C₁=C₂= about 12nanoFarad (nF). With these values, it may take about 101 nanoseconds forthe circuit to go through an I_(MIN) of −67.4 amperes and reach anI_(MAX) of 116.9 amperes. The absolute ratio I_(MAX)/I_(MIN) wasdetermined to be about 1.73. These conditions may be sufficient for thediode to switch near the peak of the reverse current.

Example 2 Switch S

In this example, a variety of solid state switches were tested todetermine a switch that may be suitable to use for the construction ofthe pulse generator of the instant invention. Five differentcommercially available switches were purchased: one IGBT type switch(rated at 60 amperes, model number GPS60B120KD) from InternationalRectifiers (El Segundo, Calif.); three MOSFET type switches (first onerated at 13 amperes, model number APT13F120B; second one rated at 28amperes, model number APT135B2FLL; and third one rated at 37 amperes,model number APT37M100L) from Microsemi Corporation (Irvine, Calif.);and one SCR type switch (model number SK065K) from Littelfuse (Chicago,Ill.). These switches were evaluated by constructing a circuit shown inFIG. 1 with L₁=L₂= about 250 nH and C₁=C₂= about 12 nF. The diode D wasreplaced with a short wire. The short circuit current was measured witha current transformer. The peak of the forward current was recorded foreach switch, and plotted against the input voltage.

The results are shown in FIG. 7. APT37M100L MOSFETs (about 1 kV, about37 amperes DC rated) manufactured by Microsemi Corporation operatedlinearly with up to an input of about 400 V. Thus this switch performedbetter than other switches and may be used to construct the pulsegenerator. The maximum “on” channel resistance of this MOSFET is about0.33 ohm. It was determined that each switch can handle a half sine wavewith about 100 nanoseconds duration and a peak of about 75 amperesbefore the specified “on” resistance becomes significantly higher.

The turn-on time of the switches is limited by the MOSFET gatecapacitance, which is about 10 nF. To charge up this large capacitance,an about 9 amperes MOSFET driver IC was used for each switch. Since theinput capacitance was high, trace lengths of any wires connecting thedrivers to the gates of the MOSFETs were minimized since the inductanceinherent to the traces could be sufficiently large to induce a resonantinstability when the drivers were triggered. The gate drivers were ableto fully charge the input capacitance in about 30 nanoseconds.

In this Example, four MOSFET switches were used in parallel, each withits own driver circuit. The threshold voltage of MOSFETs exhibits apositive temperature dependence, which inhibits current hogging andmakes MOSFETs a good solid state switch for parallel operation. For indetail description of such MOSFETs, for example see: Barkhordarian,“Power MOSFET Basics,” International Rectifier, El Segundo, Calif.

Example 3 Construction of a Pulse Generator and Pulses Obtained by Usingthis Generator

In this Example, two pulse generators were designed and built by usingthe mathematical model described in Example 1. First pulse generator wasdesigned to provide a pulse with a length of about 5 nanoseconds and theother with a length of about 2.5 nanoseconds.

The pulse generators were constructed by using commercially availableEIC CN25M diodes or MURS2510 diodes (both about 1 kV, about 25 amperesDC rating). EIC CN25M diodes had about 50 nanoseconds junction recoverytime and MURS2510 diodes about 100 nanoseconds. Both diodes had veryshort snap-off times. To obtain a pulse with an amplitude of about 5.0kV with a current of about 100 amperes, five diodes were connected inseries to form a stack and five of these stacks were connected inparallel, which formed the diode array.

It was determined that, for the 5 nanosecond pulse generator, L₁=L₂=about 260 nH and C₁=C₂= about 12 nF and that, for the 2.5 nanosecondpulse generator, L₁=L₂= about 70 nH and C₁=C₂= about 33 nF. The loadR_(L) for this pulse generator was an about 50 ohms surface mountresistor.

The capacitor C₁ was charged to the desired input voltage by a highvoltage about 6 kW power supply with a model name Xantrex XPR 600-10600V. Four APT37M100L MOSFET type switches were used in parallel as theswitch S. Each MOSFET switch was driven by an about 9 amperes integratedcircuit. These MOSFET drivers were powered by a low voltage about 90 Wpower supply with a model name Sorenson LS 30-3 30 V. The pulsegenerator was triggered by an Agilent 33120A waveform generator. Theoutput pulse was monitored by Tektronix DPO 4104 1 GHz oscilloscope. Thevoltage and the current of nanosecond pulses were measured by a powermeasurement device, which was explained in detail in Krishnaswamy etal., “Compact Subnanosecond High Voltage Pulse Generation System ForCell Electro-Manipulation”, U.S. Patent Application No. 2008/0231337 andSanders et al., “Broadband Power Measurement of High-Voltage, NanosecondElectric Pulses for Biomedical Applications,” IEEE International PowerModulator Conference, Las Vegas, Nev., 2008, pages 350-353. Paragraphs339 to 363 and FIGS. 44 to 47 of the patent application publication ofKrishnaswamy et al. are incorporated herein by reference.

The pulse generators were operated at a repetition rate of about 1 kHzwith resistive charging. High repetition rates were not a problem forthese pulse generators given the small size of the first capacitor C₁.The 6 kW power supply was excessive given that only about 4.32 mJ wasneeded to charge the capacitor C₁= about 12 nF at input voltage of about600 V. At a repetition rate of about 1 kHz, this energy corresponds toabout 4.32 W of average power. With a high current power supply,repetition rates well in excess of 1 kHz may be reached if the chargingresistor is replaced with a high current choke or resonant chargingnetwork.

First, the input voltage V_(in) was varied in the range of 100 V to 600V and the variation of the pulse amplitude V_(max) was measured. Resultsare shown in FIG. 8. For the pulse generator with the inductances L₁=L₂=about 260 nH, the pulse amplitude increased somewhat linearly withincreasing input voltage. However, for the pulse generator with theinductances L₁=L₂= about 70 nH, the pulse amplitude increase with inputvoltage was somewhat non-linear. Particularly for the input voltagesabove 200 V, the slope of the curve decreased, possibly caused by thelosses occurring in the pulse generator.

In order to determine causes of these losses, the short circuit currentwas measured. This measured current was compared to the short circuitcurrent calculated in Example 1. The results are shown in FIG. 9. Themeasured current closely matches the calculated current. The period fromI_(MIN) to I_(MAX) for the measured current, about 119 nanoseconds waslonger than that of the calculated current, about 109 nanoseconds. Thisdiscrepancy was probably due to the added inductance of the currenttransformer used for the measurement. The absolute ratio ofI_(MAX)/I_(MIN) for the measured current, about 1.66 was slightly lowerthan that of the calculated current, about 1.73. This might be a resultof the sub-ohm on resistance of the MOSFET switches. The close match ofthe measured response to the calculated response indicated that the lossin output amplitude was probably caused by the diodes.

The diodes may reduce the pulse amplitude if their junction recoverytime is significantly different from the peak (i.e. I_(MAX)) time of thereverse current, or if they dissipate a significant amount of the totalpulse energy as they turn off.

To determine the cause of the output amplitude loss, the diodes werereplaced with a short circuit and the current of this pulse generatorwas measured. Results of this measurement were compared withmeasurements of the current flowing through the diodes in FIG. 10. Thesemeasurements indicated that the diodes were in fact switching open nearthe peak of the reverse current. Thus, it was concluded that the loss inamplitude might be a result of energy dissipation during the diodeswitching process.

Smaller inductance values of L₁ and L₂ may translate to higher peakcurrents through the diodes, which would imply that output pulseamplitudes may be increased by manufacturing diodes with reduced energylosses. In practice, after the reverse current through a single diodestack surpasses 50 amperes, the losses in the switching process mayincrease non-linearly, and the output amplitude may be consequentlyaffected. Even when the current is below 50 amperes per diode stack, thefinite rise-time of the pulse may cause the peak amplitude to besignificantly less than that calculated by the model described above.

FIG. 11 shows an output pulse obtained from the pulse generatorconstructed with the inductances L₁=L₂= about 260 nH and thecapacitances C₁=C₂= about 12 nF. The input voltage V_(in) was about 600V and the load R_(L) was about 50 ohms. The pulse amplitude V_(max)obtained from this pulse generator was about 3.48 kV and the pulselength reported at the full-width-at-half-maximum (FWHM) was about 4.8nanoseconds. This measured pulse amplitude of about 3.48 kV was about67% lower than the calculated amplitude of about 5.85 kV, which wouldhave been obtained if the diode losses could be reduced to negligiblelevels. In spite of this limitation, it was demonstrated that carefulchoice of inductor and capacitor values may yield a pulse generator withan output amplitude that may scale with the input voltage.

FIG. 12 shows an output pulse obtained from the pulse generatorconstructed with the inductances L₁=L₂= about 70 nH and the capacitancesC₁=C₂= about 33 nF. The input voltage V_(in) was about 600 V and theload R_(L) was about 50 ohms. The pulse amplitude V_(max) obtained fromthis pulse generator was about 1.016 kV and the FWHM was about 2.6nanoseconds.

This example demonstrated that pulses with amplitudes exceeding 1 kV andthe FWHMs shorter than 100 nanoseconds may be obtained by having thepulse generators of the instant invention. This example furtherdemonstrated that these pulse generators may provide pulses withamplitudes that may be scaled with the input voltage.

Example 4 Repeatability and Jitter

In this Example, the jitter and the repeatability of one of the pulsegenerators of Example 3 were determined. This pulse generator wasconstructed with the inductances L₁=L₂= about 260 nH and thecapacitances C₁=C₂= about 12 nF. The input voltage V_(in) was about 700V and the load R_(L) was about 50 ohms. FIG. 13 shows traces of 25pulses obtained by using this pulse generator. In this figure, the pulsetraces were superimposed over one another. The pulse amplitude obtainedfrom this pulse generator was about 4.40 kV and the pulse lengthreported at the FWHM was about 5.3 nanoseconds.

As these results indicated, there was no recognizable jitter. Pulse topulse deviation of the amplitude and the FWHM was also negligible. Thisexample demonstrated that the pulse generators of this invention mayprovide desired pulses repeatedly with negligible jitter and deviation.

Example 5 Input-Output Linearity of the Pulse Generators

In this Example, the input and output linearity of one of the pulsegenerators of Example 3 were further determined. This pulse generatorwas constructed with the inductances L₁=L₂= about 260 nH and thecapacitances C₁=C₂= about 12 nF. The input voltage V_(in) was about 700V and the load R_(L) was about 50 ohms.

As shown in FIG. 14, the pulse amplitude increased with increasing inputvoltage. The ratio of the output amplitude to the input voltage (i.e.multiplication factor) increased somewhat linearly with increasing inputvoltage up to about 500 V. Then, above 500 V, this ratio started todecrease. This decrease may be due to losses from MOSFETs used as switchS. Adding more MOSFETs in parallel to the pulse generator of thisexample may mitigate this problem.

This example demonstrated that the pulse generators of this inventionmay provide pulses with amplitudes that may be scaled with the inputvoltage.

Example 6 Construction of a Pulse Generators

In this Example, a construction of a pulse generator circuitschematically shown in FIG. 1 was demonstrated.

In this construction, the pulse generator includes a junction recoverydiode S, wherein the anode side of the diode S is connected to theground, a second inductor L₂ connected to the cathode side of the diode,a second capacitor C₂ connected in series with the second inductor L₂,first terminal of a first inductor L₁ connected to the second terminalof the second capacitor C₂, second terminal of the first inductor L₁connected to the ground, first terminal of a first capacitor C₁connected to first terminal of the first inductor L₁ as well as thesecond terminal of the second capacitor C₂, first terminal of a switch Sconnected to the second terminal of the first capacitor C₁, secondterminal of the switch S connected to the ground. A load R_(L) may beconnected in series with the diode S.

In this construction, every component of the circuit may be a singlecomponent or may be an array of the component. For example, the firstcapacitor C₁ may be a single capacitor or a capacitor array. Thesearrays may be constructed by connecting each component in series and/orin parallel. For example, the capacitor array may be constructed byconnecting more than one capacitor in series and/or in parallel.

The components, steps, features, objects, benefits and advantages thathave been discussed above are merely illustrative. None of them,including the discussions relating to them, are intended to limit thescope of protection in any way. Numerous other embodiments are alsocontemplated, including embodiments that have fewer, additional, and/ordifferent components, steps, features, objects, benefits and advantages.The components and steps may also be arranged and ordered differently.

For example, although diodes, capacitances, inductances, resistances andswitches have been illustrated in the drawings and/or discussed assingle components, they may instead each be made of multiple components,cooperating together to perform the illustrated or recited function.

In short, the scope of protection is limited solely by the claims thatnow follow. That scope is intended to be as broad as is reasonablyconsistent with the language that is used in the claims and to encompassall structural and functional equivalents. Nothing that has been statedor illustrated is intended to cause a dedication of any component, step,feature, object, benefit, advantage, or equivalent to the public,regardless of whether it is recited in the claims.

1. A pulse generator circuit for delivering a short high current pulse to a load comprising: a diode configured to store charges in its depletion layer when there is a forward flow of a current and to rapidly switch open after the depletion layer is substantially discharged by a reverse flow of a current; a switch configured to allow storage of energy from a source when it is opened and to allow the forward current flow after it is closed; a first resonant circuit configured to store energy from the source when the switch is opened and to provide the forward current flow through the diode after the switch is closed, thereby charging the depletion layer of the diode; a second resonant circuit configured to store the energy transferred from the first resonant circuit after the switch is closed and to provide the reverse current flow through the diode until the depletion layer of the diode is substantially discharged, thereby causing the diode to rapidly switch open, and thereafter to provide a reverse current to the load; and an electrical component configured to limit damage to the pulse generator circuit, wherein said electrical component is selected from a group consisting of a current limiting resistor, a terminating resistance and combinations thereof.
 2. The pulse generator circuit of claim 1, wherein the pulse generator is configured to cause the charges stored in the depletion layer of the diode to be substantially discharged when the peak current flowing through the second resonant circuit is substantially higher than the peak current that previously flowed through the first resonant circuit.
 3. The pulse generator circuit of claim 1, wherein the pulse generator is configured to cause the charges stored in the depletion layer of the diode to be substantially discharged when the ratio of the peak of the reverse flow of the current to the peak of the forward flow of the current is substantially approaching to two.
 4. The pulse generator circuit of claim 1, wherein the diode is configured to operate in a junction recovery mode.
 5. The pulse generator circuit of claim 1, wherein the diode is configured to operate in a silicon opening switch mode.
 6. The pulse generator circuit of claim 1, wherein the diode has a junction recovery time longer than 10 nanoseconds.
 7. The pulse generator circuit of claim 1, wherein the diode has a junction recovery time longer than 25 nanoseconds.
 8. The pulse generator circuit of claim 1, wherein the diode is configured to have a snap-off time shorter than 10 percent of its junction recovery time.
 9. The pulse generator circuit of claim 1, wherein the diode is configured to store charges in its depletion layer with an amount higher than one micro-coulomb.
 10. The pulse generator circuit of claim 1, wherein the first resonant circuit includes an inductor.
 11. The pulse generator circuit of claim 10, wherein the inductor is an air-core inductor, linear-magnetic-core inductor, saturable-magnetic-core inductor or combinations thereof.
 12. The pulse generator circuit of claim 10, wherein the inductor is an air-core inductor.
 13. The pulse generator circuit of claim 1, wherein the second resonant circuit includes an inductor.
 14. The pulse generator circuit of claim 13, wherein the inductor is an air-core inductor, linear-magnetic-core inductor, saturable-magnetic-core inductor or combinations thereof.
 15. The pulse generator circuit of claim 13, wherein the inductor is an air-core inductor.
 16. The pulse generator circuit of claim 1, wherein the resonant frequency of the first resonance circuit and the resonant frequency of the second resonance circuit are substantially the same.
 17. The pulse generator circuit of claim 1, wherein the resonant frequency of the first resonance circuit and the resonant frequency of the second resonance circuit are substantially different.
 18. The pulse generator circuit of claim 1, wherein the switch has a turn-on time of less than 100 nanoseconds.
 19. The pulse generator circuit of claim 1, wherein the switch is a metal-oxide semiconductor field effect transistor switch, integrated gate bipolar transistor switch, bipolar junction transistor switch, silicon controlled rectifier switch, gas discharge switch, or combinations thereof.
 20. The pulse generator circuit of claim 1, wherein the electrical component configured to limit damage to the pulse generator circuit is a current limiting resistor.
 21. The pulse generator circuit of claim 1, wherein the electrical component configured to limit damage to the pulse generator circuit is a terminating resistance.
 22. The pulse generator circuit of claim 1, wherein the pulse generator further comprises a transformer configured to isolate the pulse generator circuit.
 23. The pulse generator circuit of claim 1, wherein the pulse generator is configured to generate at least one pulse that is having a length of no more than 100 nanoseconds at the full-width-at-half-maximum and an amplitude of at least 1 kV. 